Long Noncoding RNA AB074169 Inhibits Cell Proliferation via Modulation of KHSRP-Mediated CDKN1a Expression in Papillary Thyroid Carcinoma

Gou, Qinglong; Gao, Linbo; Nie, Xinwen; Pu, Wenchen; Zhu, Jingqiang; Wang, Yichao; Liu, Xuesha; Tan, Shuangyan; Zhou, Jian‐Kang; Gong, Yanqiu; He, Jinzhi; Wu, Ke; Xie, Yuxin; Zhao, Wanjun; Dai, Lunzhi; Liu, Lunxu; Xiang, Rong; Wei, Yuquan; Zhang, Lin; Peng, Yong

doi:10.1158/0008-5472.can-17-3766

Cited by 74 publications

(48 citation statements)

References 29 publications

(34 reference statements)

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“…This study provides orthogonal evidence supporting a protumorigenic role of KHSRP in CRC, on the basis of extensive mining of multiple publicly available data sets, analysis of patient samples, and in vitro cell line models. Our results are in agreement with recent reports in osteosarcoma, 13 lung cancer, 12,54 papillary thyroid cancer, 55 and esophageal squamous cell carcinoma. 56 The IHC data provide evidence for KHSRP overexpression in the context of both primary tumor and metastasis.…”

Section: Discussionsupporting

confidence: 94%

KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment

Caiazza

Oficjalska

Tosetto

et al. 2019

The American Journal of Pathology

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KH-type splicing regulatory protein (KHSRP) is a multifunctional nucleic acid binding protein implicated in key aspects of cancer cell biology: inflammation and cell-fate determination. However, the role KHSRP plays in colorectal cancer (CRC) tumorigenesis remains largely unknown. Using a combination of in silico analysis of large data sets, ex vivo analysis of protein expression in patients, and mechanistic studies using in vitro models of CRC, we investigated the oncogenic role of KHSRP. We demonstrated KHSRP expression in the epithelial and stromal compartments of both primary and metastatic tumors. Elevated expression was found in tumor versus matched normal tissue, and these findings were validated in larger independent cohorts in silico. KHSRP expression was a prognostic indicator of worse overall survival (hazard ratio, 3.74; 95% CI, 1.43e22.97; P Z 0.0138). Mechanistic data in CRC cell line models supported a role of KHSRP in driving epithelial cell proliferation in both a primary and metastatic setting, through control of the G 1 /S transition. In addition, KHSRP promoted a proangiogenic extracellular environment by regulating the secretion of oncogenic proteins involved in diverse cellular processes, such as migration and response to cellular stress. Our study provides novel mechanistic insight into the tumor-promoting effects of KHSRP in CRC.

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Section: Discussionsupporting

confidence: 94%

KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment

Caiazza

Oficjalska

Tosetto

et al. 2019

The American Journal of Pathology

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“…Many lncRNAs are related to PTC, and their functions have been examined in recent studies. For example, lncRNA AB074169 could regulate cell proliferation by modulating KHSRP‐mediated p21 expression in thyroid cells and functions as a tumor suppressor during PTC tumorigenesis . The lncRNA NEAT1 promotes carcinogenesis and undesirable progression of PTC by modulating miR‐129‐5p/KLK7 expression .…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA RP11‐547D24.1 regulates proliferation and migration in papillary thyroid carcinoma: Identification and validation of a novel long noncoding RNA through integrated analysis of TCGA database

et al. 2019

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Long noncoding RNAs (lncRNAs) are known to be key regulators of numerous biological processes, and substantial evidence supports that abnormal lncRNA expression plays a significant role in tumorigenesis and tumor progression. However, the mechanism by which lncRNAs function in thyroid carcinoma are still unclear. To investigate the role of lncRNAs in the tumorigenesis of papillary thyroid carcinoma (PTC), we analyzed lncRNA data in The Cancer Genome Atlas RNA‐Seq database. A comparison of lncRNAs in cancerous thyroid tissues and normal tissues revealed hundreds of differentially expressed lncRNAs. Of 7589 lncRNAs identified in 561 thyroid cancer cases (503 cancerous tissues and 58 normal tissues), the expression levels of 144 were found to be aberrant (|log2 fold change| >2 and adjusted P < 0.05). The top 10 lncRNAs with the most significant differences were LINC01977, RP11‐363E7.4, RP3‐483K16.4, RP11‐547D24.1, RUNDC3A‐AS1, AC093609.1, CTD‐2008L17.2, HAGLROS, UNC5B‐AS1, and LINC01354. In addition, CTD‐2008L17.2, HAGLROS, AC093609.1, UNC5B‐AS1, and RUNDC3A‐AS1 were shown to play vital roles in determining the histological cancer type. Furthermore, RP11‐547D24.1 and UNC5B‐AS1 could distinguish patients with different stages of PTC. The lncRNA RP11‐547D24.1 was validated by loss‐of‐function assays, revealing that downregulation of this lncRNA regulates thyroid tumor cell proliferation and apoptosis, invasion, and migration. This study demonstrates the potential for using lncRNAs to interpret the pathogenesis and development of PTC.

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“…For example, high expression of lncRNA colon cancerassociated transcript-1 (CCAT1) in esophageal squamous cell carcinoma is caused by H3K27 acetylation-mediated activation, whereas decreased expression of p53-induced lncRNA TP53 target 1 (TP53TG1) is due to high methylation of its gene promoter. 33 Like other tumors, some abnormally expressed lncRNAs were found in cancer tissues of primary lung cancer, and some of them were highly expressed in NSCLC. 34,35 LINC01194 is an up-and-coming lncRNA that…”

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confidence: 99%

<p>The lncRNA LINC01194/miR-486-5p Axis Facilitates Malignancy in Non-Small Cell Lung Cancer via Regulating CDK4</p>

Xing¹,

Zhang²,

Gao³

et al. 2020

OTT

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Background: This experimental design was based on lncRNA LINC01194 to explore the pathogenesis of NSCLC. Methods: RT-qPCR was used to detect the expression of lncRNA LINC01194 and miR-486-5p in NSCLC tissues and cell lines. CCK-8, colony formation, and transwell assays were used to examine the effects of lncRNA LINC01194 and miR-486-5p on NSCLC cell proliferation and migration invasiveness. For target gene prediction and screening, luciferase reporter assays were used to verify downstream target genes for lncRNA LINC01194 and miR-486-5p. The protein expression of CDK4 was detected using Western blotting. The tumor changes in mice were detected by in vivo experiments in nude mice. Results: LncRNA LINC01194 was highly expressed in NSCLC tissues and NSCLC lines (A549, H1299, H460 cells, H1975), and lncRNA LINC01194 significantly promoted cell proliferation and migration of NSCLC cells. MiR-486-5p was identified as a potential target for LINC01194, and miR-486-5p was expressed at a low level in NSCLC tissues and NSCLC lines (A549, H1299, H460 cells, H1975). CDK4 was identified as a potential target for miR-486-5p. LncRNA LINC01194 was able to inhibit miR-486-5p expression and upregulate the expression level of CDK4. Finally, the results of in vivo animal models confirmed that lncRNA LINC01194 promoted NSCLC progression by modulating the miR-486-5p/CDK4 axis. Conclusion: LncRNA LINC01194 promoted the progression of NSCLC by modulating the miR-486-5p/CDK4 axis.

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Long Noncoding RNA AB074169 Inhibits Cell Proliferation via Modulation of KHSRP-Mediated CDKN1a Expression in Papillary Thyroid Carcinoma

Cited by 74 publications

References 29 publications

KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment

KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment

Long noncoding RNA RP11‐547D24.1 regulates proliferation and migration in papillary thyroid carcinoma: Identification and validation of a novel long noncoding RNA through integrated analysis of TCGA database

<p>The lncRNA LINC01194/miR-486-5p Axis Facilitates Malignancy in Non-Small Cell Lung Cancer via Regulating CDK4</p>

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